A recent study, using a liver-specific Cb1r knockout mouse model, demonstrated that peripheral Cb1r could be selectively targeted for the treatment of fatty liver, impaired glucose homeostasis, and dyslipidemia to reduce the neuropsychiatric side effects of nonselective Cb1r signaling blockade in treatment of obesity-associated conditions [9] thereby demonstrating the beneficial actions of blocking the CB1R signaling pathway to restore hepatic metabolic homeostasis. Here, CNR1 is linked to fatty liver disease.